Compounds with a 4-phenylchroman skeleton and a phenyl ring at the 3 position with particular emphasis on the nature of the cis-trans configuration of the substituents at the 3 and 4 position (locants are according to the rules of Chemical Abstracts) are described in WO 98/18771 for estrogenic therapies. Although there is a keen interest in compounds with affinity for the estrogen receptor, new compounds with a 4-benzyl-2-phenylchroman skeleton and affinity for the estrogen receptor cannot be learnt from this document.
The interest in new compounds with affinity for the estrogen receptor stems from unsatisfactory results with known estrogenic compounds for osteoporosis treatment and treatment of other postmenopausal complaints and from the discovery of two distinct types of receptors, denoted ERα and ERβ (see Mosselman et al., FEBS Letters 392 (1996) 49-53 as well as EP-A-0 798 378). Since these receptors have a different distribution in human tissue, the finding of compounds which possess a selective affinity for either of the two is an important technical progress, making it possible to provide a more selective treatment in estrogen-receptor related medical treatments, such as those for contraception and for treatment of menopausal complaints, osteoporosis, and estrogen dependent tumour control, with a lower burden of estrogen-related side-effects.